Adenomyosis: genetics of estrogen metabolism

Abstract

Background To analyze the allelic variants of genes of enzymes involved in estrogen metabolism: CYP1A1, CYP1A2, CYP19 and SULT1A1 using polymerase chain reaction-restriction fragment length polymorphism-restriction fragment length polymorphism (PCR-RFLP) analysis of women with histologically confirmed adenomyosis and women without proliferative diseases of pelvic organs was performed. We studied the following polymorphisms: CYP1A1 M1, T264 → C transition in the 3′-noncoding region; CYP1A2*1F, C734 → A transversion in CYP1A2 gene; C → T transition (Arg264Cys) in exon 7 of CYP19; SULT1A1*2, G638 → A transition (Arg213His) in the SULT1A1 gene. Materials and methods The study included 804 patients. Group I (experimental group) consisted of 268 women with adenomyosis. Inclusion criteria were: histological verification of adenomyosis, consent of patients to participate in the study. Group II (control group) – 536 women without proliferative diseases of the uterus. Inclusion criteria were: lack of proliferative processes of the uterus histologically confirmed by ultrasound examination, patient’s consent to participate in the study. Results We found the significant association of C allele, T/C and C/C genotypes of the CYP1A1 gene (CYP1A1 M1 polymorphism), A allele, C/A and A/A genotypes of the CYP1A2 gene (CYP1A2*1F polymorphism) and the T allele, C/T and C/C genotypes of the CYP19 (Arg264Cys polymorphism) gene with the risk for adenomyosis. Conclusions Patients with adenomyosis had increased frequency of C allele, T/C and C/C genotypes of the CYP1A1 gene, A allele, C/A and A/A genotypes of the CYP1A2 gene and T allele and C/T and C/C genotypes of the CYP19 gene and, on the contrary, decreased frequency of the mutant allele and heterozygous and mutant homozygous genotype of the CYP1A2 gene compared to women without proliferative diseases of the uterus.

Adenomyosis: Mechanisms and Pathogenesis

“…78 Notably, patients with adenomyosis have increased frequency of the C allele in the T/C and C/C genotypes of the CYP1A1 gene, A allele in the C/A and A/A genotypes of the CYP1A2 gene, and the T allele and C/T and C/C genotypes of the CYP19 gene compared with women without adenomyosis. 79 Additionally, COMT 158 G/A gene polymorphisms contribute to the high risk of developing adenomyosis, particularly in Asian populations. 80 These results further demonstrate the role of polymorphisms of estrogen metabolism genes in adenomyosis.…”

Uterine Adenomyosis: From Disease Pathogenesis to a New Medical Approach Using GnRH Antagonists

“…The exact mechanisms governing hyperestrogenism in adenomyosis still need to be elucidated, but genetic predisposition is suspected. One study identified differential alleles in key genes involved in estrogen metabolism in women with adenomyosis compared with the control group [ 44 ]. Aberrant expression of ERs may also be the underlying cause of dysregulated estrogen signaling in the endometrium from adenomyosis subjects, as evidenced by transcriptome analysis [ 45 ].…”

Polymorphisms of CYP1A1, CYP1A2, CYP19, and SULT1A1 genes in women with early miscarriage

“…При возникновении мутации C→А в 734 положении от старта транскрипции наблюдается снижение активности фермента и соответствующего белка. Следовательно, наличие дикого аллеля определяет более высокую активность этого фермента, что может приводить к увеличению фонового уровня эстрогенов вследствие медленной скорости их окисления до неактивных продуктов метаболизма и вызывать состояние гиперэстрогенемии [4,5,7,9].…”

“…В последнее время увеличивается количество исследований, связанных с поиском и характеристикой полиморфных вариантов ДНК в кодирующих и некодирующих районах генов, в той или иной степени вовлеченных в канцерогенез. Эти исследования показывают, что полиморфизм ДНК даже вне кодирующей области может быть связан с ослаблением или усилением функции гена [7,8].…”